Prostaglandin E receptor 3 promotes the dysfunction of vascular smooth muscle cells induced by platelet-derived growth factor via regulating PI3K/Akt pathway

Abstract

BACKGROUND AND OBJECTIVE: The dysfunction of vascular smooth muscle cells (VSMCs)contributes to the pathogenesis of atherosclerosis, which is associated with coronary heart disease and acutemyocardial infarction (AMI). This study is conducted to explain the biological function of prostaglandin Ereceptor 3 (EP3) in regulating the phenotypes of VSMCs.MATERIALS AND METHODS: Platelet-derived growth factor-BB (PDGF-BB) was used to treatVSMCs to construct the cell model. qPCR was performed to examine the expression of EP3 in the VSMCsafter PDGF-BB treatment. After EP3 was silenced, inhibited or overexpressed in VSMCs, CCK-8 assay,BrdU assay, flow cytometry and Transwell assay were performed to detect the viability, proliferation, cellcycle progression and migration of VSMCs. In addition, the expression levels of PI3K, p-p85, Akt, p-Aktin VSMCs was measured by Western blotting.RESULTS: The expression of EP3 in VSMCs is promoted by PDGF-BB treatment in a time- and dosedependentmanner. EP3 overexpression facilitates the viability, proliferation and migration of VSMCswhile silencing EP3 or pharmacological inhibition of EP3 represses the dysfunction of VSMCs inducedby PDGF-BB. EP3 promoted phosphorylation of p85, Akt (Ser473) and Akt (Thr308) in VSMCs, and thepromoting effects of EP3 on the viability, proliferation, migration and cell cycle progression of VSMCswere counteracted after PI3K signalling was inhibited.CONCLUSION: EP3 participates in inducing the dysfunction of VSMCs induced by PDGF viaregulating PI3K/Akt pathway, suggesting EP3 is a therapeutic target for atherosclerosis, AMI and othercardiovascular diseases.